The American journal of surgical pathology
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Am. J. Surg. Pathol. · Feb 2016
Case ReportsCombined "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma" Harboring IDH1 R132H and BRAF V600E Mutations.
Pleomorphic xanthoastrocytoma (PXA) has rarely been reported in combination with infiltrating glioma, historically interpreted as a "collision tumor." Isocitrate dehydrogenase 1 (IDH1) and BRAF V600E mutations are usually not concurrent. The former is typical of adult infiltrating gliomas, and the latter is identified in a variety of primary central nervous system neoplasms, including PXA, ganglioglioma, pilocytic astrocytoma, and rarely infiltrating gliomas. We report the case of a 56-year-old man presenting with seizures and headaches. ⋯ On sequencing of the 2 components separately after microdissection, both showed identical IDH1 R132H and TP53 R273C point mutations, whereas the BRAF V600E mutation was limited to the PXA-like component. These findings are consistent with clonal expansion of a morphologically distinct focus, harboring a private BRAF V600E mutation within an IDH1-mutant glioma. Intratumoral heterogeneity and clonal evolution, as seems to have occurred here, suggest reevaluation of "collision tumors" as a concept.
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Am. J. Surg. Pathol. · Jan 2016
Multicenter Study Comparative StudyDenosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone.
Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. ⋯ Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little resemblance to their pretreatment counterparts, careful attention to the history of denosumab administration is crucial to avoid a misdiagnosis with an important impact on therapy. Unlike malignant GCTs, tGCTs lack significant nuclear atypia, mitotic activity, and infiltration of preexisting bone, but instead show a unique pattern of intralesional bone deposition.
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Am. J. Surg. Pathol. · Dec 2015
Comparative StudyIgG4-related Orbital Disease and Its Mimics in a Western Population.
Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). ⋯ These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic inflammation and fibrosis involving lacrimal gland or soft tissue (12 cases), and others. Clinical and pathologic findings among our patients with IgG4-RD involving the orbit are similar to those previously described in Asian patients. Careful evaluation of histologic and immunophenotypic features and clinical correlation are required to distinguish orbital IgG4-RD from other sclerosing inflammatory lesions in the orbit.
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Am. J. Surg. Pathol. · Dec 2015
Case Reports Multicenter StudyRadiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always Derived From the Primary Tumor.
Desmoid-type fibromatosis is a rare, highly infiltrative, locally destructive neoplasm that does not metastasize, but recurs often after primary surgery. Activation of the Wnt/β-catenin pathway is the pathogenic mechanism, caused by an activating mutation in exon 3 of CTNNB1 (85% of the sporadic patients). Radiotherapy is a frequent treatment modality with a local control rate of approximately 80%. ⋯ Three patients showed a CTNNB1 hotspot mutation (T41A, S45F, or S45N) in both the desmoid-type fibromatosis and the radiation-induced sarcoma. The other 3 patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2 with a T41A and 1 with an S45F mutation), which was absent in the sarcoma. In conclusion, postradiation sarcomas that occur in the treatment area of desmoid-type fibromatosis are extremely rare and can arise through malignant transformation of CTNNB1-mutated desmoid fibromatosis cells, but may also originate from CTNNB1 wild-type normal cells lying in the radiation field.
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Idelalisib is an inhibitor of the PI3Kδ isoform approved for treatment of patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Many patients develop gastrointestinal symptoms during idelalisib therapy; however, the pathologic effects of this drug have not been characterized. We identified 50 patients who received at least 3 months of idelalisib therapy. ⋯ Idelalisib commonly causes diarrheal symptoms in patients undergoing therapy for B-cell neoplasia, which may be severe in nearly 20% of patients. Characteristic histologic features include the combination of intraepithelial lymphocytosis and crypt cell apoptosis, often accompanied by neutrophils. Discontinuation of the drug results in symptomatic improvement and resolution of histologic changes.